Filoviruses (e.g., Ebola virus (EBOV) and Marburg virus (MARV)) are among the most lethal and destructive viruses. They cause severe, often fatal viral hemorraghic fevers in humans and nonhuman primates (e.g., monkeys, gorillas, and chimpanzees). Filoviruses are of particular concern as possible biological weapons since they have the potential for aerosol dissemination and weaponization.
The incubation period for Filovirus infection ranges from 2 to 21 days. The onset of illness is abrupt and is characterized by high fever, headaches, joint and muscle aches, sore throat, fatigue, diarrhea, vomiting, and stomach pain. A rash, red eyes, hiccups and internal and external bleeding may be seen in some patients. Within one week of becoming infected with the virus, most patients experience chest pains and multiple organ failure, go into shock, and die. Some patients also experience blindness and extensive bleeding before dying.
Filoviridae are a family of RNA viruses. Two members of the Filoviridae family have been identified: EBOV and MARV. There is one identified strain of MARV and four identified subtypes (i.e., strains) of EBOV: Ebola-Zaire, Ebola-Sudan, Ebola-Ivory Coast (i.e., Ebola-Tai), and Ebola-Reston. The exact origin, locations, and natural habitat of Filoviridae are unknown. However, on the basis of available evidence and the nature of similar viruses, it is postulated that Filoviridae are zoonotic (i.e., animal-borne) and are normally maintained in an animal host that is native to the African continent.
For more than 30 years, EBOV has been associated with periodic episodes of hemorrhagic fever in Central Africa that produce severe disease in infected patients. Mortality rates in outbreaks have ranged from 50% for the Sudan species of EBOV (SEBOV) to up to 90% for the Zaire species of EBOV (ZEBOV) (Sanchez et al., Filoviridae: Marburg and Ebola Viruses, in Fields Virology (eds. Knipe, D. M. & Howley, P. M.) 1409-1448 (Lippincott Williams & Wilkins, Philadelphia)). An outbreak late in 2007 caused by an apparently new species of EBOV in Uganda resulted in a fatality rate of about 25% (Towner et al., PLoS Pathog., 4:e1000212 (2008)). ZEBOV has also decimated populations of wild apes in this same region of Africa (Walsh et al., Nature, 422:611-614 (2003)).
Prevention and treatment of EBOV infections presents many challenges. In fact, there are no vaccines or postexposure treatment modalities available for preventing or managing EBOV infections. Patients instead receive supportive therapy, i.e., electrolyte and fluid balancing, oxygen, blood pressure maintenance, and treatment for any secondary infections.
Thus, there is a need for compositions and methods for treating and preventing EBOV infections, e.g., by specifically modulating EBOV gene expression. The present invention addresses these and other needs.